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Trial By Error, Continued: My Libelous Blogging on Virology Blog

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by David Tuller

During a recent talk at the annual conference of the British Renal Society, pediatrician and staunch PACE proponent Esther Crawley accused me of libeling her. I wasn’t at her presentation, but her slides were captured and tweeted. Dr. Crawley’s lecture recounted her heroic struggle against the dark forces of anti-science—presumably, those pesky ME/CFS advocates who challenge her work. One slide included a mention of “libellous blogs,” along with a screen shot of one of my Virology Blog posts. Hm.

This libelous Virology Blog post—“Trial By Error, Continued: The New FITNET Trial for Kids”–was about Dr. Crawley’s flawed research into ME/CFS and her proposed study of Internet-based cognitive behavior therapy for kids. The post explained how Dr. Crawley’s research conflates “chronic fatigue” and “chronic fatigue syndrome,” thus dramatically increasing the apparent prevalence of the illness. In the post, I also took aim at Dr. Crawley’s FITNET-NHS protocol and an earlier Dutch study of the same online intervention. I will not review the arguments here, but everything I wrote was based on facts.

In that post and elsewhere, I have expressed my strong opinion, as a public health academic and professional, that Dr. Crawley’s research is misleading. In pushing that perspective, I have used sharp and snarky rhetoric to ensure my voice was heard. Maybe I’ve even been obnoxious. But that just makes me sharp, snarky and obnoxious. It does not make me libelous. Something has to be untrue for it to be libelous, and Dr. Crawley has not identified any actual errors in my work.

It’s not surprising that Dr. Crawley would dislike my opinions and find them offensive. But my opinions are fair comment and based on my interpretations of the documented facts. There is an appropriate legal remedy for libel, and it is not to stand in front of a crowd of nephrologists and make baseless but serious accusations. Dr. Crawley should know better. And she should vet her slides with lawyers before she pulls a stunt like that again.

Having now informed Britain’s community of renal experts that I have engaged in libelous blogging—and that my colleague, Dr. Vincent Racaniello, has engaged in libelous blog-publishing–Dr. Crawley should explain herself. Several days ago, I asked her via e-mail to provide evidence for her accusation; in other words, to tell me what is inaccurate in my posts. I offered, of course, to correct any inaccuracies—something I do even when I’m not being accused of libel. I offered to run any statement she sent as part of my post, without editing or trimming it. Dr. Crawley did not respond to my e-mail.

In addition to her position as a professor of child health at the University of Bristol, Dr. Crawley is deputy chair of the CFS/ME Research Collaborative (CMRC). Her reckless accusation of libel raises questions about her judgment, and it certainly casts a shadow over any organization in which she plays a leadership role. I have e-mailed the other members of the CMRC board to express my dismay at Dr. Crawley’s accusation. I have also asked them to publicly disavow it.

To be sure, Dr. Crawley might feel under pressure at the moment, having recently suffered a humiliating public setback. She is deeply involved in the ME/CFS Epidemiology and Genomics Alliance, or MEGA, an ambitious proposed research project that grew out of a CMRC initiative. In March, MEGA announced that the Wellcome Trust had rejected its preliminary application for funding, meaning the group was not invited to submit a full proposal.

Wellcome is a major source of non-governmental funding for health and medical research, so this rejection of the MEGA application is a huge blow. Although the reasons for Wellcome’s rejection were not disclosed, we can speculate on some of the possibilities. Perhaps the application from Dr. Crawley and her colleagues was simply sub-par–poorly argued or inadequate for any number of reasons. It is possible the Wellcome reviewers were perplexed at the MEGA request, since the project’s goal of collecting samples from ME/CFS patients appears similar to what a respected and well-established organization, the U.K. ME/CFS Biobank, is already doing successfully. It would be reasonable for Wellcome to wonder whether funding a completely new parallel project for the same illness would be an effective use of their resources. I assume other grant-makers might have similar questions.

Another intriguing possibility is that the Wellcome reviewers have actually gotten wind of the growing international controversy over the PACE trial. Perhaps they recognize that the evidence base behind the CBT/GET approach is fast eroding, now that many experts outside the orbit of Dr. Crawley, Sir Simon Wessely, and the Science Media Centre have reviewed the study and assessed it harshly.  Given the changing attitudes, the Wellcome reviewers might even have wondered why Dr. Crawley still defends PACE so vigorously, as when she told an interviewer late last year that it was a “great, great” trial.

Whatever the reason for Wellcome’s rejection of the MEGA application, the bad news for PACE supporters keeps coming. In March, more than 100 scientists, clinicians and other experts–from Berkeley, Columbia, Stanford, Harvard, University College London, King’s College London, and elsewhere–signed an open letter to Psychological Medicine. (I helped organize the open letter, and also signed it.) The open letter, posted on Virology Blog, demanded retraction of the “recovery” findings published by Psychological Medicine in 2013. In outlining the study’s multiple missteps, the open letter bluntly declared that “such flaws are unacceptable in published research; they cannot be defended or explained away.”

Given Dr. Crawley’s recent endorsement of PACE’s greatness, does she consider all the signatories of that open letter to be libelous, or just me? It is likely that many if not all of those experts would agree with my opinion that Dr. Crawley’s research conflates “chronic fatigue” and “chronic fatigue syndrome” in a misleading manner. Would that qualify all of them as libelous?

Fortunately for the patient community, scientific and academic concern over the PACE enterprise continues to build. The Journal of Health Psychology (JHP) has just published a series of blistering commentaries—or perhaps libelous, depending on your perspective–about what is now being referred to as “PACE-gate.” The commentaries reflect the genuine surprise in the broader research community at PACE’s methodological lapses. No one, it seems, has ever before come across a clinical trial in which, as in PACE, participants could actually be “recovered” on key outcomes at baseline, before any treatment at all.

The JHP is based in the U.K., so publication of the commentaries represents a welcome departure from the stubborn, longstanding reluctance of the British academic and media establishments to seriously question the PACE investigators and their supporters, like Dr. Crawley, on scientific grounds. Hopefully medical journals and news organizations will soon start conducting their own independent investigations into this huge, publicly funded disaster. Maybe they will even ask why the entire U.K. medical establishment accepts as legitimate a clinical trial in which participants could be simultaneously defined as disabled enough for entry and yet “recovered” on key outcomes. (My own JHP commentary focuses on how the PACE investigators offer non-answers instead of answers, and then claim to have answered all of the questions.)

No matter how many times they try, PACE proponents are unable to provide credible and logical explanations for the irregularities of the research—at least, credible enough to make the questions disappear. Instead, they have accused critics of this and that malfeasance, all the while complaining about being persecuted themselves. I understand the urgency behind their increasingly strained and even laughable efforts to defend this indefensible body of research—these scientists are fighting for their reputations. But they are losing that fight because they are so clearly wrong on the science. In disseminating false accusations of libel, Dr. Crawley has merely embarrassed herself and exposed the desperation and intellectual weakness of the position she is seeking to defend.

Intestinal dysbiosis in ME/CFS patients

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AlistipesThe microbes that live on and in us provide a host of functions that are essential for our health. Changes in the composition of these microbial communities correlate with a variety of disease states. Results of a new study (link) reveal altered populations of intestinal bacteria and metabolic disturbances in ME/CFS patients.

The study subjects were 50 patients with ME/CFS from four sites across the US (meeting 1994 CDC Fukuda and 2003 Canadian consensus criteria) and 50 healthy controls. Some of the ME/CFS patients (21/50) reported a diagnosis of irritable bowel syndrome, absent in all the controls. Whether IBS leads to ME/CFS or is a consequence is unclear.

Genomic DNA was extracted from a fecal sample from each patient and subjected to high-throughput sequencing. Bacterial sequences were identified after computational subtraction of human genomic, mitochondrial, and ribosomal sequences.

The results show that bacterial taxa in ME/CFS patients with and without IBS were distinct. The most reliable markers of ME/CFS with IBS were increased abundance of Alistipes (pictured) and a decrease in Faecalibacterium genera of bacteria. In contrast, an increase in Bacteriodes and a decrease in Bacteroides vulgatus were associated with ME/CFS without IBS.

The bacterial genes identified in the sequence analysis were used to predict alterations in metabolic pathways. Some pathways are altered only in ME/CFS patients, while others are linked to IBS. Enrichment in the pathway of vitamin B6 biosynthesis appeared to be independent of IBS. This vitamin plays a role in many aspects of metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and more, and is a cofactor for many essential reactions.

The unsaturated fatty acid biosynthesis pathway was also found to be reduced in ME/CFS patients independent of IBS. A reduction of specific fatty acids has been linked to pro-inflammatory responses and immune activation in ME/CFS patients.

These and other metabolic findings in ME/CFS patients validate additional work on bacterial metabolic pathways and the metabolome - the set of small-molecule chemicals – of ME/CFS patients.

Others have previously shown increased levels of cytokines in the plasma and cerebrospinal fluid of ME/CFS patients who had been ill for a short period of time. No such association was found in the current study, perhaps because most subjects had been ill for extended periods of time.

The dysbiosis and bacterial metabolic disturbances identified in this study of ME/CFS patients are intriguing. The results suggest that abundance of certain bacterial taxa could be used as diagnostic markers for the disease. The more important question is whether these changes are a cause or a consequence of ME/CFS. Answering this question is relevant to the potential for using microbiome transplants, or metabolic therapeutic strategies to ameliorate the disease.

An open letter to Psychological Medicine, again!

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Last week, Virology Blog posted an open letter to the editors of Psychological Medicine. The letter called on them to retract the misleading findings that participants in the PACE trial for ME/CFS had “recovered” from cognitive behavior therapy and graded exercise therapy. More than 100 scientists, clinicians, other experts and patient organizations signed the letter.

Three days later, I received a response from Sir Robin Murray, the UK editor of Psychological Medicine. Here’s what he wrote:

 Thank you for your letter and your continuing interest in the paper on the PACE Trial which Psychological Medicine published. I was interested to learn that Wilshire and colleagues have now published a reanalysis of the original data from the PACE Trial in the journal Fatigue: Biomedicine, Health & Behavior, a publication that I was not previously aware of. Presumably, interested parties will now be able to read this reanalysis and compare the scientific qualiity of the re-analysis with that of the original. My understanding is that this is the way that science advances.

This is an unacceptable response.  Sir Robin Murray is misguided if he believes that science advances by allowing misleading claims based on manipulated data to stand in the literature. When researchers include participants who were already “recovered” on key indicators at baseline, the findings are by definition so flawed and nonsensical they must be retracted.

That the editors of Psychological Medicine do not grasp that it is impossible to be “disabled” and “recovered” simultaneously on an outcome measure is astonishing and deeply troubling. It is equally astonishing that the PACE authors now defend themselves, as noted in a New York Times opinion piece on Sunday, by arguing that this overlap doesn’t matter because there were also other recovery criteria.

In response to the comments from Psychological Medicine, we are reposting the open letter with 17 added individuals and 24 more organizations, for a total of 142 signatories altogether. These include two lawyers from Queen Mary University of London, the academic home of lead PACE investigator Peter White, along with other experts and ME/CFS patient groups from around the world.

 

Sir Robin Murray and Dr. Kenneth Kendler
Psychological Medicine
Cambridge University Press
University Printing House
Shaftesbury Road
Cambridge CB2 8BS
UK

Dear Sir Robin Murray and Dr. Kendler:

In 2013, Psychological Medicine published an article called “Recovery from chronic fatigue syndrome after treatments given in the PACE trial.”[1] In the paper, White et al. reported that graded exercise therapy (GET) and cognitive behavioural therapy (CBT) each led to recovery in 22% of patients, compared with only 7% in a comparison group. The two treatments, they concluded, offered patients “the best chance of recovery.”

PACE was the largest clinical trial ever conducted for chronic fatigue syndrome (also known as myalgic encephalomyelitis, or ME/CFS), with the first results published in The Lancet in 2011.[2] It was an open-label study with subjective primary outcomes, a design that requires strict vigilance to prevent the possibility of bias. Yet PACE suffered from major flaws that have raised serious concerns about the validity, reliability and integrity of the findings.[3] Despite these flaws, White et al.’s claims of recovery in Psychological Medicine have greatly impacted treatment, research, and public attitudes towards ME/CFS.

According to the protocol for the PACE trial, participants needed to meet specific benchmarks on four different measures in order to be defined as having achieved “recovery.”[4] But in Psychological Medicine, White et al. significantly relaxed each of the four required outcomes, making “recovery” far easier to achieve. No PACE oversight committees appear to have approved the redefinition of recovery; at least, no such approvals were mentioned. White et al. did not publish the results they would have gotten using the original protocol approach, nor did they include sensitivity analyses, the standard statistical method for assessing the impact of such changes.

Patients, advocates and some scientists quickly pointed out these and other problems. In October of 2015, Virology Blog published an investigation of PACE, by David Tuller of the University of California, Berkeley, that confirmed the trial’s methodological lapses.[5] Since then, more than 12,000 patients and supporters have signed a petition calling for Psychological Medicine to retract the questionable recovery claims. Yet the journal has taken no steps to address the issues.

Last summer, Queen Mary University of London released anonymized PACE trial data under a tribunal order arising from a patient’s freedom-of-information request. In December, an independent research group used that newly released data to calculate the recovery results per the original methodology outlined in the protocol.[6] This reanalysis documented what was already clear: that the claims of recovery could not be taken at face value.

In the reanalysis, which appeared in the journal Fatigue: Biomedicine, Health & Behavior, Wilshire et al. reported that the PACE protocol’s definition of “recovery” yielded recovery rates of 7 % or less for all arms of the trial. Moreover, in contrast to the findings reported in Psychological Medicine, the PACE interventions offered no statistically significant benefits. In conclusion, noted Wilshire et al., “the claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments.”

In short, the PACE trial had null results for recovery, according to the protocol definition selected by the authors themselves. Besides the inflated recovery results reported in Psychological Medicine, the study suffered from a host of other problems, including the following:

*In a paradox, the revised recovery thresholds for physical function and fatigue–two of the four recovery measures–were so lax that patients could deteriorate during the trial and yet be counted as “recovered” on these outcomes. In fact, 13 % of participants met one or both of these recovery thresholds at baseline. White et al. did not disclose these salient facts in Psychological Medicine. We know of no other studies in the clinical trial literature in which recovery thresholds for an indicator actually represented worse health status than the entry thresholds for serious disability on the same indicator.

*During the trial, the authors published a newsletter for participants that included glowing testimonials from earlier participants about their positive outcomes in the trial.[7] An article in the same newsletter reported that a national clinical guidelines committee had already recommended CBT and GET as effective; the newsletter article did not mention adaptive pacing therapy, an intervention developed specifically for the PACE trial. The participant testimonials and the newsletter article could have biased the responses of an unknown number of the two hundred or more people still undergoing assessments—about a third of the total sample.

*The PACE protocol included a promise that the investigators would inform prospective participants of “any possible conflicts of interest.” Key PACE investigators have had longstanding relationships with major insurance companies, advising them on how to handle disability claims related to ME/CFS. However, the trial’s consent forms did not mention these self-evident conflicts of interest. It is irrelevant that insurance companies were not directly involved in the trial and insufficient that the investigators disclosed these links in their published research. Given this serious omission, the consent obtained from the 641 trial participants is of questionable legitimacy.

Such flaws are unacceptable in published research; they cannot be defended or explained away. The PACE investigators have repeatedly tried to address these concerns. Yet their efforts to date—in journal correspondence, news articles, blog posts, and most recently in their response to Wilshire et al. in Fatigue[8]—have been incomplete and unconvincing.

The PACE trial compounded these errors by using a case definition for the illness that required only one symptom–six months of disabling, unexplained fatigue. A 2015 report from the U.S. National Institutes of Health recommended abandoning this single-symptom approach for identifying patients.[9] The NIH report concluded that this broad case definition generated heterogeneous samples of people with a variety of fatiguing illnesses, and that using it to study ME/CFS could “impair progress and cause harm.”

PACE included sub-group analyses of two alternate and more specific case definitions, but these case definitions were modified in ways that could have impacted the results. Moreover, an unknown number of prospective participants might have met these alternate criteria but been excluded from the study by the initial screening.

To protect patients from ineffective and possibly harmful treatments, White et al.’s recovery claims cannot stand in the literature. Therefore, we are asking Psychological Medicine to retract the paper immediately. Patients and clinicians deserve and expect accurate and unbiased information on which to base their treatment decisions. We urge you to take action without further delay.

Sincerely,

Dharam V. Ablashi, DVM, MS, Dip Bact
Scientific Director
HHV-6 Foundation
Former Senior Investigator
National Cancer Institute
National Institutes of Health
Bethesda, Maryland, USA

James N. Baraniuk, MD
Professor, Department of Medicine
Georgetown University
Washington, D.C., USA

Lisa F. Barcellos, MPH, PhD
Professor of Epidemiology
School of Public Health
California Institute for Quantitative Biosciences
University of California, Berkeley
Berkeley, California, USA

Lucinda Bateman, MD
Medical Director
Bateman Horne Center
Salt Lake City, Utah, USA

Alison C. Bested, MD, FRCPC
Clinical Associate Professor
Faculty of Medicine
University of British Columbia
Vancouver, British Columbia, Canada

Molly Brown, PhD
Assistant Professor
Department of Psychology
DePaul University
Chicago, Illinois, USA

John Chia, MD
Clinician and Researcher
EVMED Research
Lomita, California, USA

Todd E. Davenport, PT, DPT, MPH, OCS
Associate Professor
Department of Physical Therapy
University of the Pacific
Stockton, California, USA

Ronald W. Davis, PhD
Professor of Biochemistry and Genetics
Stanford University
Stanford, California, USA

Simon Duffy, PhD, FRSA
Director
Centre for Welfare Reform
Sheffield, UK

Jonathan C.W. Edwards, MD
Emeritus Professor of Medicine
University College London
London, UK

Derek Enlander, MD
New York, New York, USA

Meredyth Evans, PhD
Clinical Psychologist and Researcher
Chicago, Illinois, USA

Kenneth J. Friedman, PhD
Associate Professor of Physiology and Pharmacology (retired)
New Jersey Medical School
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, USA

Robert F. Garry, PhD
Professor of Microbiology and Immunology
Tulane University School of Medicine
New Orleans, Louisiana, USA

Keith Geraghty, PhD
Honorary Research Fellow
Division of Population Health, Health Services Research & Primary Care
School of Health Sciences
University of Manchester
Manchester, UK

Ian Gibson, PhD
Former Member of Parliament for Norwich North
Former Dean, School of Biological Sciences
University of East Anglia
Honorary Senior Lecturer and Associate Tutor
Norwich Medical School
University of East Anglia
Norwich, UK

Rebecca Goldin, PhD
Professor of Mathematics
George Mason University
Fairfax, Virginia, USA

Ellen Goudsmit, PhD, FBPsS
Health Psychologist (retired)
Former Visiting Research Fellow
University of East London
London, UK

Maureen Hanson, PhD
Liberty Hyde Bailey Professor
Department of Molecular Biology and Genetics
Cornell University
Ithaca, New York, USA

Malcolm Hooper, PhD
Emeritus Professor of Medicinal Chemistry
University of Sunderland
Sunderland, UK

Leonard A. Jason, PhD
Professor of Psychology
DePaul University
Chicago, Illinois, USA

Michael W. Kahn, MD
Assistant Professor of Psychiatry
Harvard Medical School
Boston, Massachusetts, USA

Jon D. Kaiser, MD
Clinical Faculty
Department of Medicine
University of California, San Francisco
San Francisco, California, USA

David L. Kaufman, MD
Medical Director
Open Medicine Institute
Mountain View, California, USA

Betsy Keller, PhD
Department of Exercise and Sports Sciences
Ithaca College
Ithaca, New York, USA

Nancy Klimas, MD
Director, Institute for Neuro-Immune Medicine
Nova Southeastern University
Director, Miami VA Medical Center GWI and CFS/ME Program
Miami, Florida, USA

Andreas M. Kogelnik, MD, PhD
Director and Chief Executive Officer
Open Medicine Institute
Mountain View, California, USA

Eliana M. Lacerda, MD, MSc, PhD
Clinical Assistant Professor
Disability & Eye Health Group/Clinical Research Department
Faculty of Infectious and Tropical Diseases
London School of Hygiene & Tropical Medicine
London, UK

Charles W. Lapp, MD
Medical Director
Hunter-Hopkins Center
Charlotte, North Carolina, USA
Assistant Consulting Professor
Department of Community and Family Medicine
Duke University School of Medicine
Durham, North Carolina, USA

Bruce Levin, PhD
Professor of Biostatistics
Columbia University
New York, New York, USA

Alan R. Light, PhD
Professor of Anesthesiology
Professor of Neurobiology and Anatomy
University of Utah
Salt Lake City, Utah, USA

Vincent C. Lombardi, PhD
Director of Research
Nevada Center for Biomedical Research
Reno, Nevada, USA

Alex Lubet, PhD
Professor of Music
Head, Interdisciplinary Graduate Group in Disability Studies
Affiliate Faculty, Center for Bioethics
Affiliate Faculty, Center for Cognitive Sciences
University of Minnesota
Minneapolis, Minnesota, USA

Steven Lubet
Williams Memorial Professor of Law
Northwestern University Pritzker School of Law
Chicago, Illinois, USA

Sonya Marshall-Gradisnik, PhD
Professor of Immunology
Co-Director, National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Queensland, Australia

Patrick E. McKnight, PhD
Professor of Psychology
George Mason University
Fairfax, Virginia, USA

Jose G. Montoya, MD, FACP, FIDSA
Professor of Medicine
Division of Infectious Diseases and Geographic Medicine
Stanford University School of Medicine
Stanford, California, USA

Zaher Nahle, PhD, MPA
Vice President for Research and Scientific Programs
Solve ME/CFS Initiative
Los Angeles, California, USA

Henrik Nielsen, MD
Specialist in Internal Medicine and Rheumatology
Copenhagen, Denmark

James M. Oleske, MD, MPH
François-Xavier Bagnoud Professor of Pediatrics
Senator of RBHS Research Centers, Bureaus, and Institutes
Director, Division of Pediatrics Allergy, Immunology & Infectious Diseases
Department of Pediatrics
Rutgers New Jersey Medical School
Newark, New Jersey, USA

Elisa Oltra, PhD
Professor of Molecular and Cellular Biology
Catholic University of Valencia School of Medicine
Valencia, Spain

Richard Podell, MD, MPH
Clinical Professor
Department of Family Medicine
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, USA

Nicole Porter, PhD
Psychologist in Private Practice
Rolling Ground, Wisconsin, USA

Vincent R. Racaniello, PhD
Professor of Microbiology and Immunology
Columbia University
New York, New York, USA

Arthur L. Reingold, MD
Professor of Epidemiology
University of California, Berkeley
Berkeley, California, USA

Anders Rosén, MD
Professor of Inflammation and Tumor Biology
Department of Clinical and Experimental Medicine
Division of Cell Biology
Linköping University
Linköping, Sweden

Peter C. Rowe, MD
Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, Maryland, USA

William Satariano, PhD
Professor of Epidemiology and Community Health
University of California, Berkeley
Berkeley, California, USA

Ola Didrik Saugstad, MD, PhD, FRCPE
Professor of Pediatrics
University of Oslo
Director and Department Head
Department of Pediatric Research
University of Oslo and Oslo University Hospital
Oslo, Norway

Charles Shepherd, MB, BS
Honorary Medical Adviser to the ME Association
Buckingham, UK

Christopher R. Snell, PhD
Scientific Director
WorkWell Foundation
Ripon, California, USA

Donald R. Staines, MBBS, MPH, FAFPHM, FAFOEM
Clinical Professor
Menzies Health Institute Queensland
Co-Director, National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Queensland, Australia

Philip B. Stark, PhD
Professor of Statistics
University of California, Berkeley
Berkeley, California, USA

Eleanor Stein, MD, FRCP(C)
Psychiatrist in Private Practice
Assistant Clinical Professor
University of Calgary
Calgary, Alberta, Canada

Staci Stevens, MA
Founder, Exercise Physiologist
Workwell Foundation
Ripon, California, USA

Julian Stewart, MD, PhD
Professor of Pediatrics, Physiology and Medicine
Associate Chairman for Patient Oriented Research
Director, Center for Hypotension
New York Medical College
Hawthorne, NY, USA

Leonie Sugarman, PhD
Emeritus Associate Professor of Applied Psychology
University of Cumbria
Carlisle, UK

John Swartzberg, MD
Clinical Professor Emeritus
School of Public Health
University of California, Berkeley
Berkeley, California, USA

Ronald G. Tompkins, MD, ScD
Summer M Redstone Professor of Surgery
Harvard Medical School
Boston, Massachusetts, USA

David Tuller, DrPH
Lecturer in Public Health and Journalism
University of California, Berkeley
Berkeley, California, USA

Rosemary A. Underhill, MB, BS, MRCOG, FRCSE
Physician and Independent Researcher
Palm Coast, Florida, USA

Rosamund Vallings, MNZM, MB, BS
General Practitioner
Auckland, New Zealand

Michael VanElzakker, PhD
Research Fellow, Psychiatric Neuroscience Division
Harvard Medical School & Massachusetts General Hospital
Instructor, Tufts University Psychology
Boston, Massachusetts, USA

Mark VanNess, PhD
Professor of Health, Exercise & Sports Sciences
University of the Pacific
Stockton, California, USA
Workwell Foundation
Ripon, California, USA

Mark Vink, MD
Family Physician
Soerabaja Research Center
Amsterdam, Netherlands

Frans Visser, MD
Cardiologist
Stichting Cardiozorg
Hoofddorp, Netherlands

Tony Ward, MA (Hons), PhD, DipClinPsyc
Registered Clinical Psychologist
Professor of Clinical Psychology
School of Psychology
Victoria University of Wellington
Wellington, New Zealand
Adjunct Professor, School of Psychology
University of Birmingham
Birmingham, UK
Adjunct Professor, School of Psychology
University of Kent
Canterbury, UK

William Weir, FRCP
Infectious Disease Consultant
London, UK

John Whiting, MD
Specialist Physician
Private Practice
Brisbane, Australia

Carolyn Wilshire, PhD
Senior Lecturer
School of Psychology
Victoria University of Wellington
Wellington, New Zealand

Michael Zeineh, MD, PhD
Assistant Professor
Department of Radiology
Stanford University
Stanford, California, USA

Marcie Zinn, PhD
Research Consultant in Experimental Electrical Neuroimaging and Statistics
Center for Community Research
DePaul University
Chicago, Illinois, USA
Executive Director
Society for Neuroscience and Psychology in the Performing Arts
Dublin, California, USA

Mark Zinn, MM
Research Consultant in Experimental Electrophysiology
Center for Community Research
DePaul University
Chicago, Illinois, USA

New individuals added 23 March 2017

Norman E. Booth, PhD, FInstP
Emeritus Fellow in Physics
Mansfield College
University of Oxford
Oxford, UK

Joan Crawford, CPsychol, CEng, CSci, MA, MSc
Chartered Counselling Psychologist
Chronic Pain Management Service
St Helens Hospital
St Helens, UK

Lucy Dechene, PhD
Professor of Mathematics (retired)
Fitchburg State University
Fitchburg, Massachusetts, USA

Valerie Eliot Smith
Barrister and Visiting Scholar
Centre for Commercial Law Studies
Queen Mary University of London
London, UK

Margaret C. Fernald, PhD
Clinical and Research Psychologist
University of Maine
Orono, Maine, USA

Simin Ghatineh, MSc, PhD
Biochemist
London, UK

Alan Gurwitt, M.D.
Former Clinical Child Psychiatry Faculty Member
Yale Child Study Center, New Haven, Connecticut
University of Connecticut School of Medicine, Farmington, Connecticut
Harvard Medical School, Boston, Massachusetts
Co-author of primers on Adult and Pediatric ME/CFS
Clinician in Private Practice (retired)
Boston, Massachusetts, USA

Geoffrey Hallmann, LLB, DipLegPrac
Former Laywer, (Disability And Compensation)
Lismore, Australia

Susan Levine, MD
Clinician in Private Practice
New York, New York, USA
Visiting Fellow
Cornell University
Ithaca, New York, USA

Marvin S. Medow, Ph.D.
Professor of Pediatrics and Physiology
Chairman, New York Medical College IRB
Associate Director of The Center for Hypotension
New York Medical College
Hawthorne, New York, USA

Sarah Myhill MB BS
Clinician in Private Practice
Knighton, UK

Pamela Phillips, Dip, Dip. MSc MBACP (registered)
Counsellor in Private Practice
London, UK

Gwenda L Schmidt-Snoek, PhD
Researcher
Former Assistant Professor of Psychology
Hope College
Holland, Michigan, USA

Robin Callender Smith, PhD
Professor of Media Law
Centre for Commercial Law Studies
Queen Mary University of London.
Barrister and Information Rights Judge
London, UK

Samuel Tucker, MD
Former Assistant Clinical Professor of Psychiatry
University of California, San Francisco
San Francisco, California, USA

AM Uyttersprot, MD
Neuropsychiatrist
AZ Jan Portaels
Vilvoorde, Belgium

Paul Wadeson, Bsc, MBChB, MRCGP
GP Principal
Ash Trees Surgery
Carnforth, UK

 

ME/CFS Patient Organizations

25% ME Group
UK

Emerge Australia
Australia

European ME Alliance:

Belgium ME/CFS Association
Belgium

ME Foreningen
Denmark

Suomen CFS-Yhdistys
Finland

Fatigatio e.V.
Germany

Het Alternatief
Netherlands

Icelandic ME Association
Iceland

Irish ME Trust
Ireland

Associazione Malati di CFS
Italy

Norges ME-forening
Norway

Liga SFC
Spain

Riksföreningen för ME-patienter
Sweden

Verein ME/CFS Schweiz
Switzerland

Invest in ME Research
UK

Hope 4 ME & Fibro Northern Ireland
UK

Irish ME/CFS Association
Ireland

Massachusetts CFIDS/ME & FM Association
USA

ME Association
UK

ME/cvs Vereniging
Netherlands

National ME/FM Action Network
Canada

New Jersey ME/CFS Association
USA

Pandora Org
USA

Phoenix Rising
International membership representing many countries

Solve ME/CFS Initiative
USA

Tymes Trust (The Young ME Sufferers Trust)
UK

Wisconsin ME and CFS Association
USA

New Organizations added 23 March 2017

Action CND
Canada

Associated New Zealand ME Society
New Zealand

Chester MESH (ME self-help) group
Chester, UK

German Society for ME/CFS (Deutsche Gesellschaft für ME/CFS)
Germany

Lost Voices Stiftung
Germany

M.E. Victoria Association
Canada

ME North East
UK

ME Research UK
UK

ME Self Help Group Nottingham
UK

ME/CFS and Lyme Association of WA, Inc.
Australia

ME/CFS (Australia) Ltd
Australia

ME/CFS Australia (SA), Inc.
Australia

ME/CVS Stichting Nederland
Netherlands

ME/FM Myalgic Encephalomyelitis and Fibromyalgia Society of British Columbia
Canada

MEAction
International membership representing many countries 
 
Millions Missing Canada
Canada
 
National CFIDS Foundation, Inc.
USA
 
North London ME Network
UK
 
OMEGA (Oxfordshire ME Group for Action)
UK
 
Open Medicine Foundation
USA

Quebec ME Association
Canada
 
The York ME Community
UK
 
Welsh Association of ME & CFS Support
UK
Organization added 29 March 2017
Supportgroup ME and Disability
(Steungroep ME en Arbeidsongeschiktheid)
Groningen, Netherlands

[1] White PD, Goldsmith K, Johnson AL, et al. 2013. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological Medicine 43(10): 2227-2235.

[2] White PD, Goldsmith KA, Johnson AL, et al. 2011. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The Lancet 377: 823–836

[3] Racaniello V. 2016. An open letter to The Lancet, again. Virology Blog, 10 Feb. Available at: https://www.virology.ws/2016/02/10/open-letter-lancet-again/ (accessed on 2/24/17).

[4] White PD, Sharpe MC, Chalder T, et al. 2007. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurology 7: 6.

[5] Tuller D. 2015. Trial by error: the troubling case of the PACE chronic fatigue syndrome trial. Virology Blog, 21-23 Oct. Available at: https://www.virology.ws/2015/10/21/trial-by-error-i/ (accessed on 2/24/17)

[6] Wilshire C, Kindlon T, Matthees A, McGrath S. 2016. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior; published online 14 Dec. Available at: http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724 (accessed on 2/24/17)

[7] PACE Participants Newsletter. December 2008. Issue 3. Available at: http://www.wolfson.qmul.ac.uk/images/pdfs/participantsnewsletter3.pdf (accessed on 2/24/17).

[8] Sharpe M, Chalder T, Johnson AL, et al. 2017. Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments? Fatigue: Biomedicine, Health & Behavior; published online 15 Feb. Available at: http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1288629 (accessed on 2/24/17).

[9] Green CR, Cowan P, Elk R. 2015. National Institutes of Health Pathways to Prevention Workshop: Advancing the research on myalgic encephalomyelitis/chronic fatigue syndrome. Annals of Internal Medicine 162: 860-865.

An open letter to Psychological Medicine about “recovery” and the PACE trial

by

Sir Robin Murray and Dr. Kenneth Kendler
Psychological Medicine
Cambridge University Press
University Printing House
Shaftesbury Road
Cambridge CB2 8BS
UK

Dear Sir Robin Murray and Dr. Kendler:

In 2013, Psychological Medicine published an article called “Recovery from chronic fatigue syndrome after treatments given in the PACE trial.”[1] In the paper, White et al. reported that graded exercise therapy (GET) and cognitive behavioural therapy (CBT) each led to recovery in 22% of patients, compared with only 7% in a comparison group. The two treatments, they concluded, offered patients “the best chance of recovery.”

PACE was the largest clinical trial ever conducted for chronic fatigue syndrome (also known as myalgic encephalomyelitis, or ME/CFS), with the first results published in The Lancet in 2011.[2] It was an open-label study with subjective primary outcomes, a design that requires strict vigilance to prevent the possibility of bias. Yet PACE suffered from major flaws that have raised serious concerns about the validity, reliability and integrity of the findings.[3] Despite these flaws, White et al.’s claims of recovery in Psychological Medicine have greatly impacted treatment, research, and public attitudes towards ME/CFS.

According to the protocol for the PACE trial, participants needed to meet specific benchmarks on four different measures in order to be defined as having achieved “recovery.”[4] But in Psychological Medicine, White et al. significantly relaxed each of the four required outcomes, making “recovery” far easier to achieve. No PACE oversight committees appear to have approved the redefinition of recovery; at least, no such approvals were mentioned. White et al. did not publish the results they would have gotten using the original protocol approach, nor did they include sensitivity analyses, the standard statistical method for assessing the impact of such changes.

Patients, advocates and some scientists quickly pointed out these and other problems. In October of 2015, Virology Blog published an investigation of PACE, by David Tuller of the University of California, Berkeley, that confirmed the trial’s methodological lapses.[5] Since then, more than 12,000 patients and supporters have signed a petition calling for Psychological Medicine to retract the questionable recovery claims. Yet the journal has taken no steps to address the issues.

Last summer, Queen Mary University of London released anonymized PACE trial data under a tribunal order arising from a patient’s freedom-of-information request. In December, an independent research group used that newly released data to calculate the recovery results per the original methodology outlined in the protocol.[6] This reanalysis documented what was already clear: that the claims of recovery could not be taken at face value.

In the reanalysis, which appeared in the journal Fatigue: Biomedicine, Health & Behavior, Wilshire et al. reported that the PACE protocol’s definition of “recovery” yielded recovery rates of 7 % or less for all arms of the trial. Moreover, in contrast to the findings reported in Psychological Medicine, the PACE interventions offered no statistically significant benefits. In conclusion, noted Wilshire et al., “the claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments.”

In short, the PACE trial had null results for recovery, according to the protocol definition selected by the authors themselves. Besides the inflated recovery results reported in Psychological Medicine, the study suffered from a host of other problems, including the following:

*In a paradox, the revised recovery thresholds for physical function and fatigue–two of the four recovery measures–were so lax that patients could deteriorate during the trial and yet be counted as “recovered” on these outcomes. In fact, 13 % of participants met one or both of these recovery thresholds at baseline. White et al. did not disclose these salient facts in Psychological Medicine. We know of no other studies in the clinical trial literature in which recovery thresholds for an indicator actually represented worse health status than the entry thresholds for serious disability on the same indicator.

*During the trial, the authors published a newsletter for participants that included glowing testimonials from earlier participants about their positive outcomes in the trial.[7] An article in the same newsletter reported that a national clinical guidelines committee had already recommended CBT and GET as effective; the newsletter article did not mention adaptive pacing therapy, an intervention developed specifically for the PACE trial. The participant testimonials and the newsletter article could have biased the responses of an unknown number of the two hundred or more people still undergoing assessments—about a third of the total sample.

*The PACE protocol included a promise that the investigators would inform prospective participants of “any possible conflicts of interest.” Key PACE investigators have had longstanding relationships with major insurance companies, advising them on how to handle disability claims related to ME/CFS. However, the trial’s consent forms did not mention these self-evident conflicts of interest. It is irrelevant that insurance companies were not directly involved in the trial and insufficient that the investigators disclosed these links in their published research. Given this serious omission, the consent obtained from the 641 trial participants is of questionable legitimacy.

Such flaws are unacceptable in published research; they cannot be defended or explained away. The PACE investigators have repeatedly tried to address these concerns. Yet their efforts to date—in journal correspondence, news articles, blog posts, and most recently in their response to Wilshire et al. in Fatigue[8]—have been incomplete and unconvincing.

The PACE trial compounded these errors by using a case definition for the illness that required only one symptom–six months of disabling, unexplained fatigue. A 2015 report from the U.S. National Institutes of Health recommended abandoning this single-symptom approach for identifying patients.[9] The NIH report concluded that this broad case definition generated heterogeneous samples of people with a variety of fatiguing illnesses, and that using it to study ME/CFS could “impair progress and cause harm.”

PACE included sub-group analyses of two alternate and more specific case definitions, but these case definitions were modified in ways that could have impacted the results. Moreover, an unknown number of prospective participants might have met these alternate criteria but been excluded from the study by the initial screening.

To protect patients from ineffective and possibly harmful treatments, White et al.’s recovery claims cannot stand in the literature. Therefore, we are asking Psychological Medicine to retract the paper immediately. Patients and clinicians deserve and expect accurate and unbiased information on which to base their treatment decisions. We urge you to take action without further delay.

Sincerely,

Dharam V. Ablashi, DVM, MS, Dip Bact
Scientific Director
HHV-6 Foundation
Former Senior Investigator
National Cancer Institute
National Institutes of Health
Bethesda, Maryland, USA

James N. Baraniuk, MD
Professor, Department of Medicine
Georgetown University
Washington, D.C., USA

Lisa F. Barcellos, MPH, PhD
Professor of Epidemiology
School of Public Health
California Institute for Quantitative Biosciences
University of California, Berkeley
Berkeley, California, USA

Lucinda Bateman, MD
Medical Director
Bateman Horne Center
Salt Lake City, Utah, USA

Alison C. Bested, MD, FRCPC
Clinical Associate Professor
Faculty of Medicine
University of British Columbia
Vancouver, British Columbia, Canada

Molly Brown, PhD
Assistant Professor
Department of Psychology
DePaul University
Chicago, Illinois, USA

John Chia, MD
Clinician and Researcher
EVMED Research
Lomita, California, USA

Todd E. Davenport, PT, DPT, MPH, OCS
Associate Professor
Department of Physical Therapy
University of the Pacific
Stockton, California, USA

Ronald W. Davis, PhD
Professor of Biochemistry and Genetics
Stanford University
Stanford, California, USA

Simon Duffy, PhD, FRSA
Director
Centre for Welfare Reform
Sheffield, UK

Jonathan C.W. Edwards, MD
Emeritus Professor of Medicine
University College London
London, UK

Derek Enlander, MD
New York, New York, USA

Meredyth Evans, PhD
Clinical Psychologist and Researcher
Chicago, Illinois, USA

Kenneth J. Friedman, PhD
Associate Professor of Physiology and Pharmacology (retired)
New Jersey Medical School
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, USA

Robert F. Garry, PhD
Professor of Microbiology and Immunology
Tulane University School of Medicine
New Orleans, Louisiana, USA

Keith Geraghty, PhD
Honorary Research Fellow
Division of Population Health, Health Services Research & Primary Care
School of Health Sciences
University of Manchester
Manchester, UK

Ian Gibson, PhD
Former Member of Parliament for Norwich North
Former Dean, School of Biological Sciences
University of East Anglia
Honorary Senior Lecturer and Associate Tutor
Norwich Medical School
University of East Anglia
Norwich, UK

Rebecca Goldin, PhD
Professor of Mathematics
George Mason University
Fairfax, Virginia, USA

Ellen Goudsmit, PhD, FBPsS
Health Psychologist (retired)
Former Visiting Research Fellow
University of East London
London, UK

Maureen Hanson, PhD
Liberty Hyde Bailey Professor
Department of Molecular Biology and Genetics
Cornell University
Ithaca, New York, USA

Malcolm Hooper, PhD
Emeritus Professor of Medicinal Chemistry
University of Sunderland
Sunderland, UK

Leonard A. Jason, PhD
Professor of Psychology
DePaul University
Chicago, Illinois, USA

Michael W. Kahn, MD
Assistant Professor of Psychiatry
Harvard Medical School
Boston, Massachusetts, USA

Jon D. Kaiser, MD
Clinical Faculty
Department of Medicine
University of California, San Francisco
San Francisco, California, USA

David L. Kaufman, MD
Medical Director
Open Medicine Institute
Mountain View, California, USA

Betsy Keller, PhD
Department of Exercise and Sports Sciences
Ithaca College
Ithaca, New York, USA

Nancy Klimas, MD
Director, Institute for Neuro-Immune Medicine
Nova Southeastern University
Director, Miami VA Medical Center GWI and CFS/ME Program
Miami, Florida, USA

Andreas M. Kogelnik, MD, PhD
Director and Chief Executive Officer
Open Medicine Institute
Mountain View, California, USA

Eliana M. Lacerda, MD, MSc, PhD
Clinical Assistant Professor
Disability & Eye Health Group/Clinical Research Department
Faculty of Infectious and Tropical Diseases
London School of Hygiene & Tropical Medicine
London, UK

Charles W. Lapp, MD
Medical Director
Hunter-Hopkins Center
Charlotte, North Carolina, USA
Assistant Consulting Professor
Department of Community and Family Medicine
Duke University School of Medicine
Durham, North Carolina, USA

Bruce Levin, PhD
Professor of Biostatistics
Columbia University
New York, New York, USA

Alan R. Light, PhD
Professor of Anesthesiology
Professor of Neurobiology and Anatomy
University of Utah
Salt Lake City, Utah, USA

Vincent C. Lombardi, PhD
Director of Research
Nevada Center for Biomedical Research
Reno, Nevada, USA

Alex Lubet, PhD
Professor of Music
Head, Interdisciplinary Graduate Group in Disability Studies
Affiliate Faculty, Center for Bioethics
Affiliate Faculty, Center for Cognitive Sciences
University of Minnesota
Minneapolis, Minnesota, USA

Steven Lubet
Williams Memorial Professor of Law
Northwestern University Pritzker School of Law
Chicago, Illinois, USA

Sonya Marshall-Gradisnik, PhD
Professor of Immunology
Co-Director, National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Queensland, Australia

Patrick E. McKnight, PhD
Professor of Psychology
George Mason University
Fairfax, Virginia, USA

Jose G. Montoya, MD, FACP, FIDSA
Professor of Medicine
Division of Infectious Diseases and Geographic Medicine
Stanford University School of Medicine
Stanford, California, USA

Zaher Nahle, PhD, MPA
Vice President for Research and Scientific Programs
Solve ME/CFS Initiative
Los Angeles, California, USA

Henrik Nielsen, MD
Specialist in Internal Medicine and Rheumatology
Copenhagen, Denmark

James M. Oleske, MD, MPH
François-Xavier Bagnoud Professor of Pediatrics
Senator of RBHS Research Centers, Bureaus, and Institutes
Director, Division of Pediatrics Allergy, Immunology & Infectious Diseases
Department of Pediatrics
Rutgers New Jersey Medical School
Newark, New Jersey, USA

Elisa Oltra, PhD
Professor of Molecular and Cellular Biology
Catholic University of Valencia School of Medicine
Valencia, Spain

Richard Podell, MD, MPH
Clinical Professor
Department of Family Medicine
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, USA

Nicole Porter, PhD
Psychologist in Private Practice
Rolling Ground, Wisconsin, USA

Vincent R. Racaniello, PhD
Professor of Microbiology and Immunology
Columbia University
New York, New York, USA

Arthur L. Reingold, MD
Professor of Epidemiology
University of California, Berkeley
Berkeley, California, USA

Anders Rosén, MD
Professor of Inflammation and Tumor Biology
Department of Clinical and Experimental Medicine
Division of Cell Biology
Linköping University
Linköping, Sweden

Peter C. Rowe, MD
Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, Maryland, USA

William Satariano, PhD
Professor of Epidemiology and Community Health
University of California, Berkeley
Berkeley, California, USA

Ola Didrik Saugstad, MD, PhD, FRCPE
Professor of Pediatrics
University of Oslo
Director and Department Head
Department of Pediatric Research
University of Oslo and Oslo University Hospital
Oslo, Norway

Charles Shepherd, MB, BS
Honorary Medical Adviser to the ME Association
Buckingham, UK

Christopher R. Snell, PhD
Scientific Director
WorkWell Foundation
Ripon, California, USA

Donald R. Staines, MBBS, MPH, FAFPHM, FAFOEM
Clinical Professor
Menzies Health Institute Queensland
Co-Director, National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Queensland, Australia

Philip B. Stark, PhD
Professor of Statistics
University of California, Berkeley
Berkeley, California, USA

Eleanor Stein, MD, FRCP(C)
Psychiatrist in Private Practice
Assistant Clinical Professor
University of Calgary
Calgary, Alberta, Canada

Staci Stevens, MA
Founder, Exercise Physiologist
Workwell Foundation
Ripon, California, USA

Julian Stewart, MD, PhD
Professor of Pediatrics, Physiology and Medicine
Associate Chairman for Patient Oriented Research
Director, Center for Hypotension
New York Medical College
Hawthorne, NY, USA

Leonie Sugarman, PhD
Emeritus Associate Professor of Applied Psychology
University of Cumbria
Carlisle, UK

John Swartzberg, MD
Clinical Professor Emeritus
School of Public Health
University of California, Berkeley
Berkeley, California, USA

Ronald G. Tompkins, MD, ScD
Summer M Redstone Professor of Surgery
Harvard Medical School
Boston, Massachusetts, USA

David Tuller, DrPH
Lecturer in Public Health and Journalism
University of California, Berkeley
Berkeley, California, USA

Rosemary A. Underhill, MB, BS, MRCOG, FRCSE
Physician and Independent Researcher
Palm Coast, Florida, USA

Rosamund Vallings, MNZM, MB, BS
General Practitioner
Auckland, New Zealand

Michael VanElzakker, PhD
Research Fellow, Psychiatric Neuroscience Division
Harvard Medical School & Massachusetts General Hospital
Instructor, Tufts University Psychology
Boston, Massachusetts, USA

Mark VanNess, PhD
Professor of Health, Exercise & Sports Sciences
University of the Pacific
Stockton, California, USA
Workwell Foundation
Ripon, California, USA

Mark Vink, MD
Family Physician
Soerabaja Research Center
Amsterdam, Netherlands

Frans Visser, MD
Cardiologist
Stichting Cardiozorg
Hoofddorp, Netherlands

Tony Ward, MA (Hons), PhD, DipClinPsyc
Registered Clinical Psychologist
Professor of Clinical Psychology
School of Psychology
Victoria University of Wellington
Wellington, New Zealand
Adjunct Professor, School of Psychology
University of Birmingham
Birmingham, UK
Adjunct Professor, School of Psychology
University of Kent
Canterbury, UK

William Weir, FRCP
Infectious Disease Consultant
London, UK

John Whiting, MD
Specialist Physician
Private Practice
Brisbane, Australia

Carolyn Wilshire, PhD
Senior Lecturer
School of Psychology
Victoria University of Wellington
Wellington, New Zealand

Michael Zeineh, MD, PhD
Assistant Professor
Department of Radiology
Stanford University
Stanford, California, USA

Marcie Zinn, PhD
Research Consultant in Experimental Electrical Neuroimaging and Statistics
Center for Community Research
DePaul University
Chicago, Illinois, USA
Executive Director
Society for Neuroscience and Psychology in the Performing Arts
Dublin, California, USA

Mark Zinn, MM
Research Consultant in Experimental Electrophysiology
Center for Community Research
DePaul University
Chicago, Illinois, USA

 

ME/CFS Patient Organizations

25% ME Group
UK

Emerge Australia
Australia

European ME Alliance:

Belgium ME/CFS Association
Belgium

ME Foreningen
Denmark

Suomen CFS-Yhdistys
Finland

Fatigatio e.V.
Germany

Het Alternatief
Netherlands

Icelandic ME Association
Iceland

Irish ME Trust
Ireland

Associazione Malati di CFS
Italy

Norges ME-forening
Norway

Liga SFC
Spain

Riksföreningen för ME-patienter
Sweden

Verein ME/CFS Schweiz
Switzerland

Invest in ME Research
UK

Hope 4 ME & Fibro Northern Ireland
UK

Irish ME/CFS Association
Ireland

Massachusetts CFIDS/ME & FM Association
USA

ME Association
UK

ME/cvs Vereniging
Netherlands

National ME/FM Action Network
Canada

New Jersey ME/CFS Association
USA

Pandora Org
USA

Phoenix Rising
International membership representing many countries

Solve ME/CFS Initiative
USA

Tymes Trust (The Young ME Sufferers Trust)
UK

Wisconsin ME and CFS Association
USA

[1] White PD, Goldsmith K, Johnson AL, et al. 2013. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological Medicine 43(10): 2227-2235.

[2] White PD, Goldsmith KA, Johnson AL, et al. 2011. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The Lancet 377: 823–836

[3] Racaniello V. 2016. An open letter to The Lancet, again. Virology Blog, 10 Feb. Available at: https://www.virology.ws/2016/02/10/open-letter-lancet-again/ (accessed on 2/24/17).

[4] White PD, Sharpe MC, Chalder T, et al. 2007. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurology 7: 6.

[5] Tuller D. 2015. Trial by error: the troubling case of the PACE chronic fatigue syndrome trial. Virology Blog, 21-23 Oct. Available at: https://www.virology.ws/2015/10/21/trial-by-error-i/ (accessed on 2/24/17)

[6] Wilshire C, Kindlon T, Matthees A, McGrath S. 2016. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior; published online 14 Dec. Available at: http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724 (accessed on 2/24/17)

[7] PACE Participants Newsletter. December 2008. Issue 3. Available at: http://www.wolfson.qmul.ac.uk/images/pdfs/participantsnewsletter3.pdf (accessed on 2/24/17).

[8] Sharpe M, Chalder T, Johnson AL, et al. 2017. Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments? Fatigue: Biomedicine, Health & Behavior; published online 15 Feb. Available at: http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1288629 (accessed on 2/24/17).

[9] Green CR, Cowan P, Elk R. 2015. National Institutes of Health Pathways to Prevention Workshop: Advancing the research on myalgic encephalomyelitis/chronic fatigue syndrome. Annals of Internal Medicine 162: 860-865.

Trial By Error, Continued: The Dutch Studies (Again!), and an Esther Crawley Bonus

by

By David Tuller, DrPH

David Tuller is academic coordinator of the concurrent masters degree program in public health and journalism at the University of California, Berkeley.

Wow, the research from the CBT/GET crowd in The Netherlands never ceases to amaze. Like the work of their friends in the U.K., each study comes up with new ways to be bad. It’s almost too easy to poke holes in these things. And yet the investigators appear unable to restrain themselves from making extremely generous over-interpretations of their findings–interpretations that cannot withstand serious scrutiny. The investigators always conclude, no matter what, that cognitive and/or behavioral therapies are effective for treating the disease they usually call chronic fatigue syndrome.

That this so-called science manages to get through peer review is astonishing. That is, unless we assume the studies are all peer-reviewed by other investigators who share the authors’ “unhelpful beliefs” and “dysfunctional cognitions” about ME/CFS and the curative powers of cognitive behavior therapy and graded exercise therapy.

Let’s take a quick look at yet another Dutch study of CBT for adolescents, a 2004 trial published in the BMJ. This one offers a superb example of over-interpretation. The small trial, with 71 participants, had two arms. One group received ten sessions of CBT over five months. The other received…a place on a waiting list for treatment. That’s right–they got nothing. Guess what? Those who got something did better on subjective measures at five months than those who got nothing. The investigators’ definitive conclusion: CBT is an effective treatment for sick teens.

I mean, WTF? It’s not hard to figure out that, you know, offering people some treatment is more likely to produce positive responses to subjective questions than offering them a place on a waiting list. That banal insight must be right in the first chapter of Psychological Research for Dummies. Aren’t these investigators presenting themselves as authorities on human behavior? Have they heard of something called the placebo effect?

Here’s what this BMJ study proved: Ten sessions of something lead to more reports of short-term benefits than no sessions of anything. But ten sessions of what? Maybe ten sessions of poker-playing or ten sessions of watching Seinfeld reruns while holding hands with the therapist and singing “The Girl from Ipanema” in falsetto would have produced the same results. Who knows? To flatly declare that their findings prove that CBT is an effective treatment—without caveats or an iota of caution—is a huge and unacceptable interpretive leap. The paper should never have been published in this form. It’s ridiculous to take this study as some kind of solid “evidence” for CBT.

But from the perspective of the Dutch research group, this waiting-list strategy apparently worked so well that they used it again for a 2015 study of group CBT for chronic fatigue syndrome. In this study, providing CBT in groups of four or eight patients worked significantly better than placing patients on a waiting list and providing them with absolutely nothing. Of course, no one could possibly take these findings to mean that group CBT specifically is an effective treatment—except they did.

When I’m reading this stuff I sometimes feel like I’m going out of my mind. Do I really have to pick through every one of these papers to point out flaws that a first-year epidemiology student could spot?

One big issue here is how these folks piggy-back one bad study on top of another to build what appears to be a robust body of research but is, in fact, a house of cards. When you expose the cracks in the foundational studies, the whole edifice comes tumbling down. A case in point: a 2007 Dutch study that explored the effect of CBT on “self-reported cognitive impairments and neuropsychological test performance.” Using data from two earlier studies, the investigators concluded that CBT reduced self-reported cognitive impairment but did not improve neuropsychological test performance.

Which studies was this 2007 study based on? Well, one of them was the very problematic 2004 study I have just discussed–the one that found CBT effective when compared to nothing. The other was the 2001 study in The Lancet that I wrote about in my last post. As I noted, this Lancet study claimed to be using the CDC criteria for chronic fatigue syndrome, but then waived the requirement that patients have four other symptoms besides fatigue. So it was, in effect, a study of a heterogeneous group of people suffering from at least six months of fatigue.

This case definition—six months of fatigue, with no other symptoms necessary—was used in the PACE trial and is known as the Oxford criteria. It has been discredited because it generates heterogeneous populations of people suffering from a variety of fatiguing illnesses. The results of Oxford criteria studies cannot be extrapolated to those with ME/CFS.

The 2007 study relies on the accuracy and validity of the two studies whose data it incorporates. Since those earlier studies violated basic understandings of scientific analysis, the new study is also bogus and cannot be taken seriously.

The PACE authors themselves have perfected this strategy of generating new bad papers by stacking up earlier bad ones. In November, Trudie Chalder demonstrated her personal flair for this technique as co-author of a systematic review of “attentional and interpretive bias towards illness-related information in chronic fatigue syndrome.” The authors’ conclusion: “Cognitive processing biases may maintain illness beliefs and symptoms in people with CFS.” The proposed solution to that would obviously be some sessions of CBT to correct those pesky cognitive processing biases.

Among other problems, Dr. Chalder and her co-authors included data from Oxford criteria studies. By including in the mix these heterogeneous samples of people suffering from chronic fatigue, Dr. Chalder and her colleagues have invalidated their claim that it is a study of the illness known as chronic fatigue syndrome. Of course, Psychological Medicine, which published this new research gem, is the journal that published—and has consistently refused to correct–the PACE “recovery” paper in which participants could get worse but still meet “recovery” thresholds.

The Dutch branch of the CBT/GET ideological brigade has been centered at Radboud University Nijmegen, home base for many years of two of the movement’s leading lights: Dr. Gijs Bleijenberg and Dr. Hans Knoop. Dr. Knoop recently moved to the University of Amsterdam and is currently a co-investigator of FITNET-NHS with Esther Crawley. Dr. Bleijenberg, on the occasion of his own retirement a few years ago, had this to say about his longtime friend and colleague, PACE investigator Michael Sharpe: “Dear Mike, we know each other nearly 20 years. You have inspired me very much in the way you treated CFS. Thanks a lot!”

Indeed. Dr. Bleijenberg and his Dutch colleagues appear to have learned a great deal from their PACE besties. Dr. Bleijenberg and Dr. Knoop demonstrated their own nimble use of language in the 2011 commentary in The Lancet that accompanied the publication of the first PACE results. I discussed this deceptive commentary at length in a post last year, so I won’t regurgitate the whole sorry argument here. But the Dutch investigators themselves are well aware that their claim that thirty percent of PACE participants met a “strict criterion” for recovery is preposterous.

How do I know that Dr. Bleijenberg and Dr. Knoop know this? Because as I documented in last year’s post, claims in the 2011 commentary contradict and ignore statements they themselves made in a 2007 paper that posed this question: “Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome?” (The answer, of course, was yes. Peter White, the lead PACE investigator, was a co-author of the 2007 paper.) Moreover, Dr. Bleijenberg and Dr. Knoop certainly know that the “strict criterion” they touted included thresholds that some participants had already met at baseline—yet they have still refused to correct this statement.

Given that all of these studies present serious methodological concerns, the Dutch Health Council panel considering the science of ME/CFS should be very, very wary of using them to formulate recommendations. The panel should understand that, within the next few months, peer-reviewed analyses of the original PACE data are likely to be published. (Two such analyses—one by the PACE authors themselves, one by an independent group of patients and academic statisticians–have already been published online, without peer review.) The upcoming papers will demonstrate conclusively that the “benefits” reported by the PACE team were mostly or completely illusory—and were obtained only by methodological anomalies like dramatic and unacceptable changes in outcome measures.

In an open letter to The Lancet posted on Virology Blog last February, dozens of prominent scientists and clinicians condemned the PACE study and its conclusions in harsh terms. In the U.K., the First-Tier Tribunal cited this worldwide dismay about the trial’s egregious lapses while demolishing the PACE authors’ excuses for withholding their data. The studies from the Radboud University crowd and their compatriots all rest on the same silly, unproven hypotheses of dysfunctional thinking, fear of activity, and deconditioning, and are just as intellectually incoherent and dishonest.

Should the Health Council produce a report recommending cognitive and behavioral treatments based on this laughable body of “research,” the organization could become an international joke and suffer enormous long-term reputational damage. The entire PACE paradigm is undergoing a very public unraveling. Everyone can now see what patients have seen for years. Meanwhile, biomedical researchers in the U.S., Norway, and elsewhere are narrowing in on the actual pathophysiology underlying ME/CFS.

It would be a shame to see the Dutch marching backwards to embrace scientific illiteracy and adopt an “Earth-is-flat” approach to reality.

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And for a special bonus, let’s now take another quick peek at Dr. Crawley’s work. Someone recently e-mailed me a photo of a poster presentation by Dr. Crawley and three colleagues. This poster was shown at the inaugural conference of the U.K. CFS/ME Research Collaborative, or CMRC, held in 2014. The poster was based on information from the same dataset used for Dr. Crawley’s recent Pediatrics study. As I pointed out two posts ago, that flawed study claimed a surprisingly high prevalence of 2 % among adolescents—a figure that drew widespread attention in media reports.

Dr. Crawley has cited high prevalence estimates to argue for more research into and treatment with CBT and GET. And if these prevalence rates were real, that might make sense. However, as I noted, her method of identifying the illness was specious—she decided, without justification or explanation, that she could diagnose chronic fatigue syndrome through parental and child reports of chronic fatigue, and without information from clinical examinations. In fact, after those who appeared to have high levels of depression were removed, the prevalence fell to 0.6 %–although this lower figure is not the one Dr. Crawley has emphasized.

Despite the high prevalence, however, the same dataset showed that adolescents suffering from the illness generally got better without any treatment at all, according to the 2014 poster presentation. Here’s the poster’s conclusion: “Persistent CFS/ME is rare in teenagers and most teenagers not seen in a clinical service will recovery spontaneously.”

Isn’t that great? Why haven’t I seen these hopeful data before? Although the poster predated this year’s Pediatrics paper, the data about very high rates of spontaneous recovery did not make it into that prevalence study. Moreover, the FITNET-NHS protocol and the recruitment leaflet highlight the claim that few adolescents will recover at six months without “specialist treatment” but most will recover if they receive it. Unmentioned is the highly salient fact that this “specialist treatment” apparently makes no long-term difference.

In reality, the adolescents who recovered spontaneously most likely were not suffering from ME/CFS in the first place. Dr. Crawley certainly hasn’t provided sufficient evidence that any of the children in the database she used actually had it, despite her insistence on using the term. Most likely, some unknown number of those identified as having chronic fatigue syndrome in the Pediatrics paper and in the poster presentation did have ME/CFS. But many or most were experiencing what could only be called a bout of chronic fatigue, for unknown reasons.

It is disappointing that Dr. Crawley did not include the spontaneous recovery rate in the Pediatrics paper or in the FITNET-NHS protocol. In fact, as far as I can tell, these optimistic findings have not been published anywhere. I don’t know the rationale for this decision to withhold rather than publish substantive information. Perhaps the calculation is that public reports of high rates of spontaneous recovery would undermine the arguments for ever-more funding to study CBT and GET? Just a guess, of course.

(Esther–Forgive me if I’m mistaken about whether these data have been published somewhere. I have only seen this information in your poster for the inaugural CMRC conference in 2014. If the data have been peer-reviewed and published, I stand corrected on that point and applaud your integrity.)

Trial By Error, Continued: A Follow-Up Post on FITNET-NHS

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By David Tuller, DrPH

David Tuller is academic coordinator of the concurrent masters degree program in public health and journalism at the University of California, Berkeley.

Last week’s post on FITNET-NHS and Esther Crawley stirred up a lot of interest. I guess people get upset when researchers cite shoddy “evidence” from poorly designed trials to justify foisting psychological treatments on kids with a physiological disease. I wanted to post some additional bits and pieces related to the issue.

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I sent Dr. Crawley a link to last week’s post, offering her an opportunity to send her response to Dr. Racaniello for posting on Virology Blog, along with my response to her response. So far, Dr. Racaniello and I haven’t heard back—I doubt we will. Maybe she feels more comfortable misrepresenting facts in trial protocols and radio interviews than in addressing the legitimate concerns raised by patients and confronting the methodological flaws in her research. I hope Dr. Crawley knows she will always have a place on Virology Blog to present her perspective, should she choose to exercise that option. (Esther, are you reading this?)

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From reading the research of the CBT/GET/PACE crowd, I get the impression they are all in the habit of peer-reviewing and supporting each others’ work. I make that assumption because it is hard to imagine that independent scientists not affiliated with this group would overlook all the obvious problems that mar their studies—like outcome measures that represent worse health than entry criteria, as in the PACE trial itself. So it’s not surprising to learn that one of the three principal PACE investigators, psychiatrist Michael Sharpe, was on the committee that reviewed—and approved—Dr. Crawley’s one-million-pound FITNET-NHS study.

FITNET-NHS is being funded by the U.K.’s National Institute for Health Research. I have no idea what role, if any, Dr. Sharpe played in pushing through Dr. Crawley’s grant, but it likely didn’t hurt that the FITNET-NHS protocol cited PACE favorably while failing to point out that it has been rejected as fatally flawed by dozens of distinguished scientists and clinicians. Of course, the protocol also failed to point out that the reanalyses of the trial data have shown that the findings published by the PACE authors were much better than the results using the methods they promised in their protocol. (More on the reanalyses below.) And as I noted in my previous post, the FITNET-NHS protocol also misstated the NICE guidelines for chronic fatigue syndrome, making post-exertional malaise an optional symptom rather than a required component—thus conflating chronic fatigue and chronic fatigue syndrome, just as the PACE authors did by using the overly broad Oxford criteria.

The FITNET-NHS proposal also didn’t note some similarities between PACE and the Dutch FITNET trial on which it is based. Like the PACE trial, the Dutch relied on a post-hoc definition of “recovery.” The thresholds the FITNET investigators selected after they saw the results were pretty lax, which certainly made it easier to find that participants had attained “recovery.” Also like the PACE trial, the Dutch participants in the comparison group ended up in the same place as the intervention group at long-term follow-up. Just as the CBT and GET in PACE offered no extended advantages, the same was true of the online CBT provided in FITNET.

And again like the PACE authors, the FITNET investigators downplayed these null findings in their follow-up paper. In a clinical trial, the primary results are supposed to be comparisons between the groups. Yet in the follow-up PACE and FITNET articles, both teams highlighted the “within-group” comparisons. That is, they treated the fact that there were no long-term differences between the groups as an afterthought and boasted instead that the intervention groups sustained the progress they initially made. That might be an interesting sub-finding, but to present “within-group” results as a clinical trial’s main outcome is highly disingenuous.

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As part of her media blitz for the FITNET-NHS launch, Dr. Crawley was interviewed on a BBC radio program by a colleague, Dr. Phil Hammond. In this interview, she made some statements that demonstrate one of two things: Either she doesn’t know what she’s talking about and her misrepresentations are genuine mistakes, or she’s lying. So either she’s incompetent, or she lacks integrity. Not a great choice.

Let’s parse what she said about the fact that, at long-term follow-up, there were no apparent differences between the intervention and the comparison groups in the Dutch FITNET study. Here’s her comment:

“Oh, people have really made a mistake on this,” said Dr. Crawley. “So, in the FITNET Trial, they were offered FITNET or usual care for six months, and then if they didn’t make a recovery in the usual care, they were offered FITNET again, and they were then followed up at 2 to 3 years, so of course what happened is that a lot of the children who were in the original control arm, then got FITNET as well, so it’s not surprising that at 2 or 3 years, the results were similar.”

This is simply not an accurate description. As Dr. Crawley must know, some of the Dutch FITNET participants in the “usual care” comparison group went on to receive FITNET, and others didn’t. Both sets of usual care participants—not just those who received FITNET—caught up to the original FITNET group. For Dr. Crawley to suggest that the reason the others caught up was that they received FITNET is, perhaps, an unfortunate mistake. Or else it’s a deliberate untruth.

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Another example from the BBC radio interview: Dr. Crawley’s inaccurate description of the two reanalyses of the raw trial data from the PACE study. Here’s what she said:

“First of all they did a reanalysis of recovery based on what the authors originally said they were going to do, and that reanalysis done by the authors is entirely consistent with their original results. [Actually, Dr. Crawley is mistaken here; the PACE authors did a reanalysis of “improvement,” not of “recovery”]…Then the people that did the reanalysis did it again, using a different definition of recovery, that was much much harder to reach–and the trial just wasn’t big enough to show a difference, and they didn’t show a difference. [Here, Dr. Crawley is talking about the reanalysis done by patients and academic statisticians.] Now, you know, you can pick and choose how you redefine recovery, and that’s all very important research, but the message from the PACE Trial is not contested; the message is, if you want to get better, you’re much more likely to get better if you get specialist treatment.”

This statement is at serious odds with the facts. Let’s recap: In reporting their findings in The Lancet in 2011, the PACE authors presented “improvement” results for the two primary outcomes of fatigue and physical function. They reported that about 60 percent of participants in the CBT and GET arms reached the selected thresholds for “improvement” on both measures. In a 2013 paper in the journal Psychological Medicine, they presented “recovery” results based on a composite “recovery” definition that included the two primary outcomes and two additional measures. In this paper, they reported “recovery” rates for the favored intervention groups of 22 percent.

Using the raw trial data that the court ordered them to release earlier this year, the PACE authors themselves reanalyzed the Lancet improvement findings, based on their own initial, more stringent definition of “improvement” in the protocol. In this analysis, the authors reported that only about 20 percent “improved” on both measures, using the methods for assessing “improvement” outlined in the protocol. In other words, only a third as many “improved,” according to the authors’ own original definition, compared to the 60 percent they reported in The Lancet. Moreover, in the reanalysis, ten percent “improved” in the comparison group, meaning that CBT and GET led to “improvements” in only one in ten participants—a pretty sad result for a five-million-pound trial.

However, because these meager findings were statistically significant, the PACE authors and their followers have, amazingly, trumpeted them as supporting their initial claims. In reality, the new “improvement” findings demonstrate that any “benefits” offered by CBT and GET are marginal. It is preposterous and insulting to proclaim, as the PACE authors and Dr. Crawley have, that this represents confirmation of the results reported in The Lancet. Dr. Crawley’s statement that “the message from the PACE trial is not contested” is of course nonsense. The PACE “message” has been exposed as bullshit—and everyone knows it.

The PACE authors did not present their own reanalysis of the “recovery” findings—probably because those turned out to be null, as was shown in a reanalysis of that data by patients and academic statisticians, published on Virology Blog. That reanalysis found single-digit “recovery” rates for all the study arms, and no statistically significant differences between the groups. Dr. Crawley declared in the radio interview that this reanalysis used “a different definition of recovery, that was much harder to reach.” And she acknowledged that the reanalysis “didn’t show a difference”—but she blamed this on the fact that the PACE trial wasn’t big enough, even though it was the largest trial ever of treatments for ME/CFS.

This reasoning is specious. Dr. Crawley is ignoring the central point: The “recovery” reanalysis was based on the authors’ own protocol definition of “recovery,” not some arbitrarily harsh criteria created by outside agitators opposed to the trial. The PACE authors themselves had an obligation to provide the findings they promised in their protocol; after all, that’s the basis on which they received funding and ethical permission to proceed with the trial.

It is certainly understandable why they, and Dr. Crawley, prefer the manipulated and false “recovery” data published in Psychological Medicine. But deciding post-hoc to use weaker outcome measures and then refuse to provide your original results is not science. That’s data manipulation. And if this outcome-switching is done with the intent to hide poor results in favor of better ones, it is considered scientific misconduct.

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I also want to say a few words about the leaflet promoting FITNET-NHS. The leaflet states that most patients “recover” with “specialist treatment” and less than ten percent “recover” from standard care. Then it announces that this “specialist treatment” is available through the trial—implicitly promising that most of those who get the therapy will be cured.

This is problematic for a host of reasons. As I pointed out in my previous post, any claims that the Dutch FITNET trial, the basis for Dr. Crawley’s study, led to “recovery” must be presented with great caution and caveats. Instead, the leaflet presents such “recovery” as an uncontested fact. Also, the whole point of clinical trials is to find out if treatments work—in this case, whether the online CBT approach is effective, as well as cost-effective. But the leaflet is essentially announcing the result–“recovery”—before the trial even starts. If Dr. Crawley is so sure that this treatment is effective in leading to “recovery,” why is she doing the trial in the first place? And if she’s not sure what the results will be, why is she promising “recovery”?

Finally, as has been pointed out many times, the PACE investigators, Dr. Crawley and their Dutch colleagues all appear to believe that they can claim “recovery” based solely on subjective measures. Certainly any definition of “recovery” should require that participants can perform physically at their pre-sickness level. However, the Dutch researchers refused to release the one set of data—how much participants moved, as assessed by ankle monitors called actometers–that would have proven that the kids in FITNET had “recovered” on an objective measure of physical performance. The refusal to publish this data is telling, and leaves room for only one interpretation: The Dutch data showed that participants did no better than before the trial, or perhaps even worse, on this measure of physical movement.

This FITNET-NHS leaflet should be withdrawn because of its deceptive approach to promoting the chances of “recovery” in Dr. Crawley’s study. I hope the advertising regulators in the U.K. take a look at this leaflet and assess whether it accurately represents the facts.

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As long as we’re talking about the Dutch members of the CBT/GET ideological movement, let’s also look briefly at another piece of flawed research from that group. Like the PACE authors and Dr. Crawley, these investigators have found ways to mix up those with chronic fatigue and those with chronic fatigue syndrome. A case in point is a 2001 study that has been cited in systematic reviews as evidence for the effectiveness of CBT in this patient population. (Dr. Bleijenberg, a co-investigator on the FITNET-NHS trial, was also a co-author of this study.)

In this 2001 study, published in The Lancet (of course!), the Dutch researchers described their case definition for identifying participants like this: “Patients were eligible for the study if they met the US Centers for Disease Control and Prevention criteria for CFS, with the exception of the criterion requiring four of eight additional symptoms to be present.”

This statement is incoherent. (Why do I need to keep using words like “incoherent” and “preposterous” when describing this body of research?) The CDC definition has two main components: 1) six months of unexplained fatigue, and 2) four of eight other symptoms. If you abandon the second component, you can no longer refer to this as meeting the CDC definition. All you’re left with is the requirement that participants have suffered from six months of fatigue.

And that, of course, is the case definition known as the Oxford criteria, developed by PACE investigator Michael Sharpe in the 1990s. And as last year’s seminal report from the U.S. National Institutes of Health suggested, this case definition is so broad that it scoops up many people with fatiguing illnesses who do not have the disease known as ME/CFS. According to the NIH report, the Oxford criteria can “impair progress and cause harm,” and should therefore be “retired” from use. The reason is that any results could not accurately be extrapolated to people with ME/CFS specifically. This is especially so for treatments, such as CBT and GET, that are likely to be effective for many people suffering from other fatiguing illnesses.

In short, to cite any findings from such studies as evidence for treatments for ME/CFS is unscientific and completely unjustified. The 2001 Dutch study might be an excellent look at the use of CBT for chronic fatigue*. But like FITNET-NHS, it is not a legitimate study of people with chronic fatigue syndrome, and the Dutch Health Council should acknowledge this fact in its current deliberations about the illness.

*In the original phrasing, I referred to the intervention mistakenly as ‘online CBT.’